• The Korean Journal of Physiology and Pharmacology
• /
• v.25 no.2
• /
• pp.167-175
• /
• 2021

Far-infrared rays (FIR) are known to have various effects on atoms and molecular structures within cells owing to their radiation and vibration frequencies. The present study examined the effects of FIR on gene expression related to glucose transport through microarray analysis in rat skeletal muscle cells, as well as on mitochondrial biogenesis, at high and low glucose conditions. FIR were emitted from a bio-active material coated fabric (BMCF). L6 cells were treated with 30% BMCF for 24 h in medium containing 25 or 5.5 mM glucose, and changes in the expression of glucose transporter genes were determined. The expression of GLUT3 (Slc2a3) increased 2.0-fold (p < 0.05) under 5.5 mM glucose and 30% BMCF. In addition, mitochondrial oxygen consumption and membrane potential (ΔΨm) increased 1.5- and 3.4-fold (p < 0.05 and p < 0.001), respectively, but no significant change in expression of Pgc-1a, a regulator of mitochondrial biogenesis, was observed in 24 h. To analyze the relationship between GLUT3 expression and mitochondrial biogenesis under FIR, GLUT3 was down-modulated by siRNA for 72 h. As a result, the ΔΨm of the GLUT3 siRNA-treated cells increased 3.0-fold (p < 0.001), whereas that of the control group increased 4.6-fold (p < 0.001). Moreover, Pgc-1a expression increased upon 30% BMCF treatment for 72 h; an effect that was more pronounced in the presence of GLUT3. These results suggest that FIR may hold therapeutic potential for improving glucose metabolism and mitochondrial function in metabolic diseases associated with insufficient glucose supply, such as type 2 diabetes.

• Journal of Ginseng Research
• /
• v.46 no.1
• /
• pp.156-166
• /
• 2022

Background: Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms. Methods: Inflammation model was constructed by lipopolysaccharide (LPS) in C57BL/6 mice and RAW264.7 macrophages. Molecular docking, molecular dynamics, surface plasmon resonance imaging (SPRi) and immunofluorescence were utilized to predict active component. Results: P. ginseng significantly inhibited LPS-induced lung injury and the expression of proinflammatory factors, including TNF-α, IL-6 and IL-1β. Additionally, P. ginseng blocked fluorescencelabeled LPS (LPS488) binding to the membranes of RAW264.7 macrophages, the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Furthermore, molecular docking demonstrated that ginsenoside Ro (GRo) docked into the LPS binding site of toll like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. Molecular dynamic simulations showed that the MD2-GRo binding conformation was stable. SPRi demonstrated an excellent interaction between TLR4/ MD2 complex and GRo (K_D value of 1.16 × 10^-9 M). GRo significantly inhibited LPS488 binding to cell membranes. Further studies showed that GRo markedly suppressed LPS-triggered lung injury, the transcription and secretion levels of TNF-α, IL-6 and IL-1β. Moreover, the phosphorylation of NF-κB and MAPKs as well as the p65 subunit nuclear translocation were inhibited by GRo dose-dependently. Conclusion: Our results suggest that GRo exerts anti-inflammation actions by direct inhibition of TLR4 signaling pathway.

• BMB Reports
• /
• v.55 no.11
• /
• pp.565-570
• /
• 2022

Pulmonary arterial hypertension (PAH) is a progressive and devastating disease whose pathogenesis is associated with a phenotypic switch of pulmonary arterial vascular smooth muscle cells (PASMCs). Bone morphogenetic protein (BMP) signaling and potassium two pore domain channel subfamily K member 3 (KCNK3) play crucial roles in PAH pathogenesis. However, the relationship between BMP signaling and KCNK3 expression in the PASMC phenotypic switching process has not been studied. In this study, we explored the effect of BMPs on KCNK3 expression and the role of KCNK3 in the BMP-mediated PASMC phenotypic switch. Expression levels of BMP receptor 2 (BMPR2) and KCNK3 were downregulated in PASMCs of rats with PAH compared to those in normal controls, implying a possible association between BMP/BMPR2 signaling and KCNK3 expression in the pulmonary vasculature. Treatment with BMP2, BMP4, and BMP7 significantly increased KCNK3 expression in primary human PASMCs (HPASMCs). BMPR2 knockdown and treatment with Smad1/5 signaling inhibitor substantially abrogated the BMP-induced increase in KCNK3 expression, suggesting that KCNK3 expression in HPASMCs is regulated by the canonical BMP-BMPR2-Smad1/5 signaling pathway. Furthermore, KCNK3 knockdown and treatment with a KCNK3 channel blocker completely blocked BMP-mediated anti-proliferation and expression of contractile marker genes in HPAMSCs, suggesting that the expression and functional activity of KCNK3 are required for BMP-mediated acquisition of the quiescent PASMC phenotype. Overall, our findings show a crosstalk between BMP signaling and KCNK3 in regulating the PASMC phenotype, wherein BMPs upregulate KCNK3 expression and KCNK3 then mediates BMP-induced phenotypic switching of PASMCs. Our results indicate that the dysfunction and/or downregulation of BMPR2 and KCNK3 observed in PAH work together to induce aberrant changes in the PASMC phenotype, providing insights into the complex molecular pathogenesis of PAH.

• Journal of Life Science
• /
• v.32 no.6
• /
• pp.476-481
• /
• 2022

Ubiquitin signaling regulates virtually all aspects of eukaryotic biology and dynamic processes in which protein substrates are modified by ubiquitin. To regulate these processes, deubiquitinating enzymes (DUBs) cleave ubiquitin or ubiquitin-like proteins from these substrates. DUBs have been implicated in the pathogenesis of cancer, leading to the development of increasing numbers of small-molecule DUB inhibitors. On the other hand, recent studies have focused on the function of DUBs in metabolic diseases such as obesity, diabetes, and fatty liver diseases. DUBs play a positive or negative role in the progression and development of metabolic diseases. Their involvement in cell pathology and regulation of major transcription factors in metabolic syndrome has been examined in vitro and in animal and human biopsies. UCH, USP7, and USP19 were linked to adipocyte differentiation, body weight gain, and insulin resistance in genetic or diet-induced obesity. CYLD, USP4, and USP18 were found to be closely associated with fatty liver diseases. In addition, these liver diseases were accompanied by body weight change in certain cases. Collectively, in this review, we discuss the current understanding of DUBs in metabolic diseases with a particular focus on obesity. We also provide basic knowledge and regulatory mechanisms of DUBs and suggest these enzymes as therapeutic targets for metabolic diseases.

• Journal of Mushroom
• /
• v.20 no.3
• /
• pp.178-182
• /
• 2022

Despite the long history of mushroom use, studies examining the genetic function of mushrooms and the development of new varieties via bio-molecular methods are significantly lacking compared to those examining other organisms. However, owing to recent developments, attempts have been made to use a novel gene-editing technique involving CRISPR/Cas9 technology and genetic scissors in mushroom studies. In particular, research is actively being conducted to utilize ribonucleoprotein particles (RNPs) that can be genetically edited with high efficiency without foreign gene insertion for ease of selection. However, RNPs are too large for Cas9 protein to pass through the cell membrane of the protoplasmic reticulum. Furthermore, guide RNA is unstable and can be easily decomposed, which remarkably affects gene editing efficiency. In this study, nanoparticles were used to mitigate the shortcomings of RNP-based gene editing techniques and to obtain transformants stably. We used Lentinula edodes (shiitake mushroom) Sanjo705-13 monokaryon strain, which has been successfully used in previous genome editing experiments. To identify a suitable osmotic buffer for the isolation of protoplast, 0.6 M and 1.2 M sucrose, mannitol, sorbitol, and KCl were treated, respectively. In addition, with various nanoparticle-forming materials, experiments were conducted to confirm genome editing efficiency via the formation of nanoparticles with calcium phosphate (CaP), which can be bound to Cas9 protein without any additional amino acid modification. RNPs/NP complex was successfully formed and protected nuclease activity with nucleotide sequence specificity.

• Journal of Marine Bioscience and Biotechnology
• /
• v.14 no.1
• /
• pp.1-8
• /
• 2022

This study examined the growth, fatty acid (FA) content, and carotenoids of a newly isolated freshwater microalga, Mychonastes sp. 246, in various culture media. The appropriate temperature and light intensity for culturing Mychonastes sp. 246 were determined as 18℃-22℃ and 200-250 µmol/m²/s using a high throughput photobioreactor. The microalgal cells were cultivated in 0.5 L bubble column photobioreactors using BG11, Bold's Basal media, and f/2 media. According to the growth results of the microalgae, BG11, among the tested media, showed the highest biomass concentrations (3.5 ± 0.1 g/L in 10 d). To enhance the biomass growth of the microalgae, the N:P ratio in BG11 was manipulated from 45:1 to 7:1 based on the stoichiometric cell composition. The biomass concentrations of Mychonastes sp. 246 grown on the manipulated BG11 (MBG) increased to 38% (4.6 ± 0.3 g/L in d) compared with the original BG11 (3.3 g/L). The FA content of the microalgae grown on the MBG was lower (8.4%) than that of the original BG11 (10.1%) while the FA compositions did not exhibit any significant differences. Furthermore, three kinds of carotenoids were identified in Mychonastes sp. 246, zeaxanthin, lutein, and β-carotene. These results suggest an effective strategy for increasing biomass concentrations, FA content, and carotenoids of microalgae by performing a simple N:P adjustment in the culture media.

• Korean Journal of Animal Reproduction
• /
• v.24 no.4
• /
• pp.375-383
• /
• 2000

The nuclear maturation and developmental competence of immature, oocytes collected from donors at various morphology of corpus luteum (CL) and fertilized in vitro was investigated by comparing the meiotic activity and the yields of embryos. Ovaries were divided and classified into 4 groups as the following criteria : Group 1 ; ovaries showed evidence of recent ovulation (corpus hemorragicum). Group 2 ; apex of CL was red or brown. Vasculization was limited to periphery of CL. Group 3 ; apex of CL was orange or tan. Vasculization was covered over apex of CL. Group 4 ; CL was light yellow to white and firm in texture and the vascular network on the surface of CL had disappeared. Modified TCM 199 was used for maturation in vitro of immature oocytes and development was induced by using TLP-PVA as a basic medium. When oocytes collected from each group of donors had been matured for 4, 14, and 24 hours in vitro, the proportion of oocytes reaching metaphase I and metaphase II were not different among oocytes from 4 group of ovaries. Mature metaphase II stage of oocytes in each group was first observed at 14 hours, whereas completion of maturation of. oocytes in each group was at 24 hours. Luteal morphology of ovaries had little effect on the proportion of embryos reached 2 cells and 8 cell stage. However, the proportion of embryos cleaved to morula and blastocyst stage was significantly higher in the oocytes obtained from group 1 and 3 than in the oocytes from group 2 and 4 (p＜0.05). This data suggest that reproductive status of the donor significantly influence the yield of in vitro embryos.

• Journal of Life Science
• /
• v.33 no.3
• /
• pp.287-294
• /
• 2023

Healthy adipose tissue is critical for preventing obesity by maintaining metabolic homeostasis. Adipose tissue plays an important role in energy homeostasis through glucose and lipid metabolism. Depending on nutritional status, adipose tissue expands to store lipids or can be consumed by lipolysis. The role of adipose tissue as an endocrine organ is emerging, and many studies have reported that there are various adipose tissue hormones that communicate with other organs and tissues through metabolic signaling. For example, leptin, a representative peptide hormone secreted from adipose tissues (adipokine), circulates and targets the central nervous system of the brain for appetite regression. Furthermore, adipocytes secrete inflammatory cytokines to target immune cells in adipose tissues. Not surprisingly, adipocytes can secrete fatty acid-derived hormones (lipokine) that bind to their specific receptors for paracrine and endocrine action. To understand organ crosstalk by adipose tissue hor- mones, specific metabolic signaling in adipocytes and other communicating cells should be defined. The dysfunction of metabolic signaling in adipocytes occurs in unhealthy adipose tissue in overweight and obese conditions. Therapy targeting novel adipose metabolic signaling could potentially lead to the development of an effective anti-obesity drug. This review summarizes the latest updates on adipose tissue hormone and metabolic signaling in terms of obesity and metabolic diseases.

• Journal of Life Science
• /
• v.33 no.2
• /
• pp.199-207
• /
• 2023

To prepare for the threat of a future epidemic in the post-COVID-19 era, research based on the one-health concept (i.e., the health of humans, animals, and the environment as "one") is essential. Cross-species infections are being identified as a result of the high infection rate and viral load of SARS-CoV-2 in humans. The possibility of transmission of SARS-CoV-2 from humans to mink has been determined. In addition, the transmission of SARS-CoV-2 from humans to cats through contact has been considered possible. The data so far show that livestock and poultry are less likely to be infected with SARS-CoV-2. However, if infections are established through a new mutation, the resulting diseases are expected to have enormous ripple effects on various fields, such as human food security, the economy, and trade. In addition, there are concerns about the endemic prospect of SARS-CoV-2 and the high accessibility of companion animals. This is because the evolution of the virus likely occurs in animal hosts. Once SARS-CoV-2 is established in other species, they might serve as intermediate hosts for the re-emergence of the virus in the human population. Thus, it is necessary to ensure a rapid response to future outbreaks by accumulating research data on the animal infection of SARS-CoV-2. These data can have implications for the development of animal models for vaccines and therapeutics against SARS-CoV-2. Therefore, in this study, epidemiological reviews were analyzed, and response strategies against SARS-CoV-2 infection in animals were presented using the One-health approach.

• BMB Reports
• /
• v.55 no.12
• /
• pp.609-614
• /
• 2022

Mutation of the gene for adenomatous polyposis coli (APC), as seen in Apc^Min/+ mice, leads to intestinal adenomas and carcinomas via stabilization of β-catenin. Transmembrane 4 L six family member 5 (TM4SF5) is involved in the development of non-alcoholic fatty liver disease, fibrosis, and cancer. However, the functional linkage between TM4SF5 and APC or β-catenin has not been investigated for pathological outcomes. After interbreeding Apc^Min/+ with TM4SF5-overexpressing transgenic (Tg^TM4SF5) mice, we explored pathological outcomes in the intestines and livers of the offspring. The intestines of 26-week-old dual-transgenic mice (Apc^Min/+:Tg^TM4SF5) had intramucosal adenocarcinomas beyond the single-crypt adenomas in Apc^Min/+ mice. Additional TM4SF5 overexpression increased the stabilization of β-catenin via reduced glycogen synthase kinase 3β (GSK3β) phosphorylation on Ser9. Additionally, the livers of the dualtransgenic mice showed distinct sinusoidal dilatation and features of hepatic portal hypertension associated with fibrosis, more than did the relatively normal livers in Apc^Min/+ mice. Interestingly, TM4SF5 overexpression in the liver was positively linked to increased GSK3β phosphorylation (opposite to that seen in the colon), β-catenin level, and extracellular matrix (ECM) protein expression, indicating fibrotic phenotypes. Consistent with these results, 78-week-old Tg^TM4SF5 mice similarly had sinusoidal dilatation, immune cell infiltration, and fibrosis. Altogether, systemic overexpression of TM4SF5 aggravates pathological abnormalities in both the colon and the liver.